Merisko-Liversidge Elaine M, Liversidge Gary G
Elan Drug Technologies, King of Prussia, Pennsylvania 19406, USA.
Toxicol Pathol. 2008 Jan;36(1):43-8. doi: 10.1177/0192623307310946.
More than 40% of compounds identified through combinatorial screening programs are poorly soluble in water. These molecules are difficult to formulate using conventional approaches and are associated with innumerable formulation-related performance issues. Formulating these compounds as pure drug nanoparticles is one of the newer drug-delivery strategies applied to this class of molecules. Nanoparticle dispersions are stable and have a mean diameter of less than 1 micron. The formulations consist of water, drug, and one or more generally regarded as safe excipients. These liquid dispersions exhibit an acceptable shelf-life and can be postprocessed into various types of solid dosage forms. Drug nanoparticles have been shown to improve bioavailability and enhance drug exposure for oral and parenteral dosage forms. Suitable formulations for the most commonly used routes of administration can be identified with milligram quantities of drug substance, providing the discovery scientist with an alternate avenue for screening and identifying superior analogs. For the toxicologist, the approach provides a means for dose escalation using a formulation that is commercially viable. In the past few years, formulating poorly water-soluble compounds using a nanoparticulate approach has evolved from a conception to a realization whose versatility and applicability are just beginning to be realized.
通过组合筛选程序鉴定出的化合物中，超过40%在水中溶解度较差。这些分子难以用传统方法进行制剂开发，并且存在无数与制剂相关的性能问题。将这些化合物制成纯药物纳米颗粒是应用于这类分子的较新的药物递送策略之一。纳米颗粒分散体稳定，平均直径小于1微米。制剂由水、药物和一种或多种一般认为安全的辅料组成。这些液体分散体具有可接受的保质期，并且可以后加工成各种类型的固体剂型。药物纳米颗粒已被证明可提高口服和注射剂型的生物利用度并增加药物暴露量。使用毫克量的原料药就可以确定适用于最常用给药途径的制剂，为药物研发科学家提供了一种筛选和鉴定优质类似物的替代途径。对于毒理学家而言，该方法提供了一种使用具有商业可行性的制剂进行剂量递增的手段。在过去几年中，使用纳米颗粒方法将难溶性化合物制成制剂已从概念变为现实，其通用性和适用性才刚刚开始得到认识。
